A glimpse into the structural properties of α‐synuclein oligomers

• Published in: BioFactors (Oxford) Vol. 50; no. 3; pp. 439 - 449
• Main Authors: Santos, Jaime, Pallarès, Irantzu, Ventura, Salvador
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2024
• Subjects: alpha-Synuclein - chemistry; alpha-Synuclein - genetics; alpha-Synuclein - metabolism; amyloid; Humans; oligomers; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Protein Aggregates; protein aggregation; Protein Aggregation, Pathological - genetics; Protein Aggregation, Pathological - metabolism; Protein Multimerization; α‐Synuclein; Parkinson's disease; amyloid; oligomers; protein aggregation; α‐Synuclein
• ISSN: 0951-6433; 1872-8081
• DOI: 10.1002/biof.2021

α‐Synuclein (αS) aggregation is the main neurological hallmark of a group of debilitating neurodegenerative disorders, collectively referred to as synucleinopathies, of which Parkinson's disease is the most prevalent. αS oligomers formed during the initial stages of aggregation are considered key pathogenic drivers of disease onset and progression, standing as privileged targets for therapeutic intervention and diagnosis. However, the structure of αS oligomers and the mechanistic basis of oligomer to fibril conversion are yet poorly understood, thereby precluding the rational formulation of strategies aimed at targeting oligomeric species. In this review, we delve into the recent advances in the structural and mechanistic characterization of αS oligomers. We also discuss how these advances are transforming our understanding of these elusive species and paving the way for oligomer‐targeting therapeutics and diagnosis. α‐Synuclein (αS) aggregation is central to synucleinopathies like Parkinson's disease (PD). Early‐stage αS oligomers play a key role in disease development. Their structure and conversion mechanisms are not well‐understood. This review examines recent discoveries on αS oligomers, offering valuable insights for advancing targeted therapies and diagnostics in PD.